1204669-58-8

Epacadostat is an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1) with an IC₅₀ value of 7.1 nM in HeLa cells that demonstrates little activity against the related enzymes IDO2 or tryptophan 2,3-dioxygenase (TDO). It has been shown to promote T and natural killer-cell growth, to increase IFN-γ production, and to reduce conversion to regulatory T (Treg)-like cells in a coculture system of human allogeneic lymphocytes with either dendritic cells or tumor cells. Epacadostat can also inhibit tumor growth in tumor-bearing mice in a lymphocyte-dependent manner.

Epacadostat is a potent and novel indoleamine 2,3-dioxygenase (IDO1) inhibitor with IC50 of 10 nM. It has high selectivity over IDO2 and tryptophan 2,3-dioxygenase (TDO).

IDO1

1) Liu?et al.?(2010),?Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity;?Blood?115?3520 2) Koblish?et al.?(2010),?Hydroxyamidine Inhibitors of Indolamine-2,3-dioxygenase Potently Suppress Systemic Tryptophan Catabolism and the Growth of IDO-Expressing Tumors;?Mol. Cancer Ther.?9?489 3) Jochems?et al.?(2016),?The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells;?Oncotarget?7?37762 4) Yentz and Smith (2018),?Indoleamine-2,3-dioxygenase Inhibition as a Strategy to Augment Cancer Immunotherapy;?BioDrugs?32?311 5) Zhu??et al.?(2019),?Indoleamine Dioxygenase Inhibitors: Clinical Rationale and Current Development;?Curr. Oncol. Rep.?21?2 6) Mitchell?et al.?(2018),?Epacadostat Plus Pembrolizumab in Patients with Advanced Solid Tumors: Phase I Results From a Multicenter, Open-Label Phase I/II Trial (ECHO-202/KEYNOTE-037);?J. Clin. Oncol.?36?3223